Neuropathic Pain & Complex Regional Pain Syndrome in Children Mary Rose RHSC Edinburgh Neuropathic Pain Definition Pain initiated or caused by a primary lesion or dysfunction in the nervous system Neuropathic Pain Symptoms Allodynia Pain in response to normally non-painful stimuli Hyperalgesia Increased response to noxious stimuli Spontaneous pain Shooting, electric shock Dysaesthesias Paradoxical or odd sensations Pins & needles, burning Sensory deficits Numbness, sensory loss Neuropathic Pain Aetiology Post surgery Thoracotomy Multilevel surgery for CP Lauder & White Paed Anaesth 2005 Trauma Phantom limb pain Spinal cord injury Neurological disease GuillainGuillain-Barre - 79% neuropathic pain, severe in half HMSN Korinthenberg Neuropaediatrics 2007 Hereditary Erythomelalgia – mutation affecting Na 1.7 channel Metabolic disorders Fischer & Waxman Ann NY Acad Sci 2010 Marchesoni J Pediatr 2010 Fabry’s disease – lysosomal storage disease Neuropathic pain most frequent initial complaint Treatment related 5050-90% post cisplatin 50% post vincristine Tumour involvement – peripheral / CNS CRPS Vondracek Eur J Paediatr Neurol 2009 Incidence of neuropathic pain Adults – 0.6 – 1.4% Diabetic neuropathy PHN Children – unknown Lower ? Under reporting Laborotory & clinical evidence that age at the time of injury has a role Laboratory models for neuropathic pain Spinal nerve injury Adult rats – marked allodynia P3, P10 & P21 – did not display allodynia Differences specific to neuropathic pain – mechanical allodynia displayed by very young animals exposed to inflammatory pain Howard Pain 2005 Alterations in neuro-immune response to nerve injury in the young Reduced microglial response in spinal cord Reduced T cell infiltration Reduced activation of macrophages in DRG Moss Pain 2007, Costigan J Neurosci 2009, VegaVega-Avelaira Mol Pain 2009 Variation in the incidence of neuropathic pain with age at time of injury Obstetric brachial plexus avulsion Surgical repair and testing 3-23 years later Excellent restoration of sensory function No chronic pain behaviours Anand Brain 2002 Phantom pain post amputation Amputation < 6yrs – 20% incidence of phantom pain Amputation > 6 yrs – 86% phantom pain Wilkins Pain 1998 Peripheral nerve injury upper limb <5 years – no neuropathic pain or allodynia 5-12 years – allodynia elicited on QST but no spontaneous pain >12 years – spontaneous pain Atherton J Hand Surg Eur 2008 Variation in the incidence of neuropathic pain with age at time of injury Spinal cord injury < 20 years 26% incidence in neuropathic pain vs 58% older group Post thoracotomy 0-6 yrs 3.2% - prolonged pain 7-12 yrs 19.4% - prolonged pain 13 -25 yrs 28.5% - prolonged pain 3 patients who had pain still present: surgery > 10 years Kristensen Br J Anaesth 2010 Incidence of neuralgia in UK (per 100 000) Hall Pain 2006 Neuralgia Post-herpetic Trigeminal Diabetic 0-14 yrs 1 0.4 - 15-29 yrs 4 11 1.2 30 -44 yrs 11 40 5 45-59 yrs 47 65 21 60 – 74 yrs 143 70 51 > 75 yrs 327 88 61 Management of neuropthic pain Physiotherapy/Psychology Treatment extrapolated from adult data No high level evidence Anticonvulsants Gabapentin – case reports only no RCTs in children 5-10mg/kg/dose tds Insufficient evidence for practice recommendations Golden Ped Neurol 2006 FDA warning – increased incidence of suicidal ideation and completed suicides Pregabalin Open label study, 30 children (10 -17 years), post chemo peripheral neuropathy 150 -300mg/kg daily Significant pain relief in 86%, mean decrease in VAS 59% Vondracek Eur J Paedr Neurol 2009 Lidocaine patch Case series Management of Neuropathic Pain Antidepressants Amitriptyline Evening dose – 0.5-1mg/kg Case reports only Duloxetine (SSRI) Case report – 2 adolescents diffuse pain & major depressive disorder Increase risk of suicide in < 25 yrs TENS Case reports/series Regional techniques Neuraxial/peripheral nerve blocks Complex Regional Pain Syndrome Terminology & Diagnostic Criteria – Stanton & Hicks Precipitated by noxious event (not always identifiable) Spontaneous pain or allodynia which is disproportionate in duration, severity and distribution to the expected clinical course of the inciting event Evidence at some time of autonomic dysfunction Other differential diagnoses have been excluded CRPS type 2 – associated with known peripheral nerve injury Clinical features of CRPS in children Peak incidence in early adolescence Median 12 years (6-16) Lower limb affected 60 -85% 71 – 95% female Typical high achieving Precipitating factor Minor trauma 50 -60% Major trauma or surgery 20 30% Tan Injury 2009, Tan Acta Paediatr 2008, Kachko, Kachko, Pediatr Int 2008, Low J Pediatr Orthop 2007, Sethna Pain 2007 Wilder Clin J Pain 2006 Clinical Features of CRPS in children Autonomic dysfunction Colour change 67-92% Temperature change 60-85% Swelling 33-85% Sweating 23-43% Dystrophic changes Nail/hair/skin changes Disuse Limited ROM – functional/structural Motor symptoms Dystonia, tremor, myoclonus Mild shaking to movement of whole limb Associated with prolonged symptoms & worse outcome Delay in diagnosis 2 days – 2 years Periods of non weight bearing or immobilization Multiple specialists Orthopaedic surgeons, rheumatologists, neurologists, A&E physicians Management of CRPS Explanation & Education “CRPS is a disorder of pain neurophysiology, rather than being due to ongoing tissue damage” Encourage mobilisation Physiotherapy Psychology Prospective – 6 weeks CBT & Education & Physio (intensive vs less) All improved Lee J Pediatr 2002 Drug therapy Analgesics – limited variable efficacy NSAIDs, paracetamol, tramadol, strong opioids Gabapentin Evidence of efficacy in adults Case reports only in chidren Tricyclic antidepressants Case reports only Management of CRPS – Role of interventional techniques Wide range in practice & beliefs Pain management programmes comprising purely physiotherapy & psychological techniques Sherry, Berde, Berde, Zernikow ISPP 2010 Centres that advocate early & repeated blocks UK practice Children who are failing conservative treatment Aim achieve a pain free window Must be part of a multi-modal technique Practical aspects GA US fluoroscopy guidance Catheter technique preferable to single shot Regional techniques Sympathetic blocks Lumbar Stellate Epidural IV Regional sympathetic blocks Peripheral nerve blocks Spinal cord stimulation Intrathecal LA infusions (n=1) No high level evidence – small case series Cochrane review Cepeda MS: Cochrane database 2005 Interventions in CRPS - literature Number of patients/episodes Affected limb Regional technique Outcome Meier 2009 23 23 - leg Double blind crossover Lumbar sympathetic block vs IV lidocaine Reduction pain scores & allodynia with LSB Krane 2009 25/35 27 – leg 8 - arm 8 - Epidural 16 – Sciatic nerve block 19 Lumbar sympathetic block 8 – Stellate ganglion block All blocks continuous 20 Complete resolution 8 Improvement 7 Poor response Cebrian 2009 6 6 - arm 2 peripheral nerve block 5 complete resolution 1 Poor response Kachko 2008 14 8 - leg 6 - arm 1 – Epidural 1- Stellate ganglion block (x12) 2 - Ankle block 13 full/partial recovery Dadure 2005 13 12 – leg 1 - arm Continuous PNB 12 - Popliteal 1 – Axillary All – Biers block Complete response at 2 months Currie (personal comm) 49 44 – leg 5 - arm 92 – lumbar sympathetic blocks 6 – Stellate ganglion blocks Lumbar sympathetic plexus - anatomy Anterolateral border of vertebral body Separated from sensory & motor nerves by psoas muscle Needle advanced towards side of vertebra & then redirected past the anterolateral border of vertebral body L2 – L4 Confirm position with X ray Stellate ganglion block - anatomy Fusion of 1st thoracic and inferior cervical ganglion Anterior to C7 Conveys sympathetic messages to head, neck & arm, T1 – T6 Needle inserted between trachea & carotid artery Directed towards TP of C6 Spinal Cord Stimulation – for CRPS in adolescents Low intensity electrical impulses to trigger the dorsal columns – area of intense pain replaced with paraesthesia Reversible Expensive & invasive 7 girls aged 11-14 years Severe therapy resistant CRPS Trial stimulation for 1-2 weeks before implantation of generator Analgesia developed over 2- 6 weeks – sustained at follow up 1-8 years Complete 5/7 Useful reduction 2/7 Olsson GL; EJP 2008 Which block to use No high level evidence First do no harm Least invasive – peripheral nerve blocks US guided Catheter technique Volumetric pumps Sparing of muscle power in contralateral leg Operator familiarity Indications for sympathetic block Decreasing evidence for role of sympathetic nervous system in CRPS Compared with epidural less weakness with sympathetic block – more able to undertake physical therapy Adverse effects of regional techniques Infection Haematoma Nerve damage LA toxicity Allergic reactions Encourage or reinforce a passive rather than an active role for the patient in their recovery Berde C Anesthesiology 2005 Patient may become dependent on regional blocks Placebo Effect The greater the invasiveness of the procedure the greater the placebo effect The greater the expectation for pain relief the greater will be the placebo effect The placebo tends to be of less duration Tends to be less reproducible with each successive treatment CRPS – Residual/Recurrent Symptoms Residual symptoms - incidence varies in different case series 12% symptoms at 2 years Sherry 1999 Clin J Pain 54% residual pain or dysfunction Wilder J Bone Joint Surg 1992 33% relapse, 52% ongoing pain – median follow up 12years (2-22) Tan Injury 2009 Recurrence 25-35% Majority within first 6 months after treatment CRPS -Summary Awareness & early diagnosis Avoidance of immobilisation Intensive physiotherapy with CBT – most important treatment modalities Adequate resources required Many children have disease severity that precludes their ability to tolerate PT & CBT alone First do no harm Least invasive techniques Ultimate aim of treatment is restoration of function